20-56370727-A-G

Position:

• chr20-56370727-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198437.3(AURKA):​c.855-68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,562,218 control chromosomes in the GnomAD database, including 59,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (5571 hom., cov: 32)
  • Exomes 𝑓: 0.25 (53957 hom.)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

Genes affected

AURKA (HGNC:11393): (aurora kinase A) The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKA	NM_198437.3	c.855-68T>C		intron_variant		ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.855-68T>C		intron_variant		1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35896 AN: 151932 Hom.: 5558 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.255 AC: 358963 AN: 1410168 Hom.: 53957 AF XY: 0.256 AC XY: 179563 AN XY: 702312

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.236 AC: 35912 AN: 152050 Hom.: 5571 Cov.: 32 AF XY: 0.247 AC XY: 18334 AN XY: 74320

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.245

Alfa AF: 0.239 Hom.: 7088

Bravo AF: 0.238

Asia WGS AF: 0.499 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10485805; hg19: chr20-54945783;